Commentary on cancer research, information on supplements and treatments, relevant book reviews, links to useful sites and other information that cancer sufferers, their families and friends may find useful.

‘SCAM – So-called Alternative Medicine’, is the follow-up book to ‘A Scientist In Wonderland’, Edzard Ernst’s very readable memoir. That book, reviewed here previously, Ernst told the story of how he came to be the first Professor of Complementary Medicine in the world. It was a post that was greeted enthusiastically by those who were true believers in homeopathy, healing crystals and other forms of ‘alternative medicine’. These true believers assumed that anyone taking on that role would be like minded. Unfortunately, Ernst decided that he was a scientist first and foremost and that his job meant applying the scientific method to the extraordinary claims made by practitioners. The fall out reached a peak with a very public falling out with Prince Charles and trouble for Ernst from his own university. It’s an interesting story well-told in the first book.

In this book Ernst is continuing the work that got him into so much trouble. Here he outlines how these various alternatives seem to work – their common features, imperviousness to evidence, the magical thinking and conspiracy theories that believers use to counter the lack of evidence. For example, many alternatives claim that much of contemporary medicine also doesn’t stack up and hasn’t been tested vigorously in clinical trial. While there’s a smidgen of truth there, Ernst points to the evidence that in conventional practice 80% - 90% is evidence-based (and includes the reference so you can look at the original paper itself).

While the book lacks the narrative from the first – after all that was a memoir – it does run over some of the elements of his own experience in battling with Prince Charles. It’s a book that is informed by long experience talking to people who really do believe in homeopathy and so on. Some of the people who peddle this stuff really do believe it and have the best of intentions. But there are some very cynical, mercenary people who are driven entirely by selfish reasons to exploit vulnerable people when they are sick. But perhaps, as Ernst suggests here, there’s a third group – people who convince themselves and make a nice living at the same time.

Overall this is certainly an interesting read – with plenty of useful information with which to counter fraudsters and fakes. There’s even a section on how to set yourself up as a charlatan – yep, you too can claim to cure cancer, fight dementia and tackle bad breath.

Tuesday, 20 March 2018

‘The Wisdom of Crowds’ is the name of a book by James
Surowiecki in which he discusses the idea that in certain situations aggregating
the knowledge from a random crowd of people could get to a better answer to a
problem than any single individual could – even an expert individual. It wasn’t
a new idea – according to Wikipedia (never a reliable source, so not a good ‘crowd’
example) that in 1907 Francis Galton noted that a crowd at a county fair
correctly guessed the weight of an ox when you took the average of all the
guesses. Surowiecki’s book certainly
popularised the term – I even used it in the title of a paper on drug
repurposing: ‘The wisdom of crowds and the repurposing of artesunate as ananticancer drug’ – and it has become something of a standard feature of many
books and courses in machine learning and data science.

The Nobel prize-winning economist and political scientist Frederich
von Hayek didn’t, as far as I know, use the term but the idea was central to
his thinking. He saw the price/market system as the wisdom of the crowds in
action. He saw the society as a complex and self-organised system, with distributed
decision making and dispersed knowledge as they key driving forces. Trying to
control an economy from the top down is impossible without access to all that
knowledge - knowledge that we are often not even explicitly aware that we have.

I’ve often wondered though whether it really works in
practice, or was it really the case that yet again the world is far too complex
and messy for even this simple (and surprising) idea to work. At the weekend I
finally managed to see a real world example. In the context of some fundraising
for the George Pantziarka TP53 Trust (the UK charity that supports people with
Li Fraumeni Syndrome), we attended the modern equivalent of Galton’s county
fair – a suburban Farmer’s market in south-west London. We didn’t have an ox to
spare, so in our case the crowd had to correctly guess the number of chocolate
Easter eggs to win the prize (see below, we’ll skate over the health effects of eating all
of those eggs…).

This was my chance to get my hands on a real world data set.
Unfortunately the weekend coincided with a blizzard, so turn-out was low at the
market and I was worried that the dataset wouldn’t be sufficient to show the
effect. In the end we had 66 entries – and the correct answer was 145 eggs. The
answers were all over the place, with a low of 50 and a maximum of 376 (see
scatter chart below – correct answer in red). The lucky winner got close with
an answer of 143.

So how wise was our crowd of 66? The average of the entire
data set was 144.1 – which is closer than the winning entry. I have to admit I
was surprised at just how close that is. Even more surprising is how quickly
the average converged to the correct answer. The chart below shows the
cumulative moving average converging close to the right answer within 15
guesses. That’s fast.

Was that speed of convergence just a fluke? When the dataset
is reversed what happens? The same thing – the cumulative moving average gets
close to the correct average incredibly quickly, even though it starts off with
some wildcard answers.

Although this idea might be old hat – I for one am still impressed at
these results. Although the applications for this idea are limited – it would
be great to be able to harness this sort of thing to solve something a bit more
meaningful than the size of an ox or the number of chocolate eggs. I also find
the democratic nature of this result incredibly satisfying.

Wednesday, 26 April 2017

When I wrote the NEATG model of tumour growth, published in
the journal PeerJ (https://peerj.com/articles/2176/),
I focused on the behaviour of individual cells and on the role of cell
competition and cell death in tumour growth. All models have to simplify and
abstract, and the NEATG model does exactly that. The model steered clear of the
molecular basis for the behaviour of the cells – my working assumption was that
cells produce soluble factors and signalling proteins that mediate their
cell-cell and cell-tissue interactions. It was one of the reasons I called the
model NEATG (Non-physiological Evolutionary Algorithm for Tumour Growth – though as Sebastien Benzekry pointed
out to me, the fact that the model has cells and tissues already makes it
fairly physiological… ).

Despite the level of abstraction, the model clearly does show cellular behaviours that mimic aspects of tumour growth and response to
cytotoxic chemotherapy. A surprise for me was that the model showed that accelerated tumour regrowth following
chemotherapy is driven by cell competition and the levels of cell death. I spent time looking at the research literature on these topics and found that my results were actually in line with clinically relevant phenomena – which is what makes the model interesting.

A recent paper from a group of researchers from the
University of Bologna entitled MYC, CellCompetition, and Cell Death in Cancer: The Inseparable Triad (available open access from the journal genes –
it’s well worth a read), casts some interesting light on the topic. C-Myc is
one of the most important of the master genes involved in cell cycle
progression and tissue growth. It’s a transcription factor, which means it
regulates the activity of other genes, and is often switched on permanently in
tumours rather than coming on and off as required. It’s widely associated with
a whole range of different cancers.

In this paper the authors review recent evidence from Drosophilia (fruit fly) models of cancer
and how they are implicated in cell growth, cell death and cell competition.
They outline the way that competition selects for cells that are ‘fittest’ and
that less fit cells are effectively killed off – in just the way that they do
in software in my model. The evidence that they outline suggests that one of
the drivers for the behaviour of these cells is c-Myc, making it an important
component at the physiological level missing from NEATG.The authors themselves make note of the
results from the NEATG model:

Our findings suggest that
CC [cell competition] is an innate process governing both cancer initiation and
progression, where cell death fuels the clonal expansion of the fittest cells
in the context. CC and apoptosis thus appear to be strictly linked one another,
and emerge as fundamental cancer drivers also in a computational model of
tumour growth, where several parameters of malignancy such as intra-tumour
heterogeneity and accelerated repopulation have been taken into account.

For the next stage of work on this model I will be
investigating the metabolic impact of cell growth in tumour growth, and the
impact that cell death has on this. My prediction is that the model will show
that populations of ‘super-feeders’ will emerge during tumour growth – and that
chemotherapy helps to select for these populations of cells. However, as this
stage I don’t really know that that’s what happens – I have to wait and see what
the data tells me…

In the meantime I’ll finish with some final words from the
team at Bologna :

Cells cooperate to
build an organ and, in a similar way, they cooperate to build a cancer.
Although the contexts are impressively distant, MYC-mediated cell competition
seems to be at work in both cases with the same basic, sequential elements:
cell–cell disparity in MYC contents, death of the cells with lower MYC levels,
and proliferation of the cells with higher MYC levels. This stereotypical
module shapes organ development and, possibly, cancer evolution. In growing
tumours, an excess of dying cells is known to contribute to mass expansion, but
the implication of MYC-mediated cell competition in this cancer trait has just
begun to be investigated. Further research is warranted on the intricate “life
and death” signals exchanged by confronting cell populations within the cancer
community.

Wednesday, 22 February 2017

One of the reasons for starting this website was the wish to share information with patients, carers and other people directly affected by a cancer diagnosis. The site came out of a series of discussions I had with my son George while he was in the middle of his battle against osteosarcoma. We wanted a site that could be used to share science-based information that was likely to be useful, particularly for people looking for treatment options, as we often were. However, I have to admit that in recent months the site hasn’t been getting the attention it used to – the number of new postings has been really light on the ground. One of the reasons for this has been that for a long time I had been working with the UK charity Star Throwers to produce a book that would provide a lot of that type of information in ebook and paperback form.

The Star Thowers Guide To Cancer, as the book is called, is now available via Amazon or, if you’re in Wymondham, Norfolk, direct from Star Throwers. The book covers similar ground to this website: science-based, heavy on information, concise and geared very much to looking at new treatment options. Does the world really need another new book on cancer? Book shops are full of new cancer books: memoirs, diet guides, histories of oncology and much more. But this one is different.

I like to think of this book as a ‘how to be a difficult patient’ guide. It shows you how to read the cancer literature. How to assess the breathless stories about new ‘cures’ that are frequently highlighted in the mass media. There is a detailed discussion of the tricky subject of cancer and diet. Searching for clinical trials and looking for treatments abroad are also covered in some detail. Local ablative treatments such as cryoablation are covered, including the vital information on where to look for these useful but underused treatments. Finally, there is also a chapter on drug repurposing, a topic I have covered here many times and which I now work on pretty much full-time.

In the past I have considered taking the best articles from this site and putting them together as a single download via PDF. But there’s no need now. This book provides the best of this site and much, much more.

Tuesday, 6 December 2016

Working on drug repurposing often involves an element of historical research. Drugs like cimetidine, nitroglycerin and propranolol have been around for decades and there’s a lot of good data that we can extract from old articles, clinical trials and retrospective studies. One of the best known examples of old drugs is aspirin - which is attracting a huge amount of attention from clinical researchers in oncology. There is a huge literature on aspirin, with much more on the way as clinical trials are designed, run and reported.

One of the most intriguing things about aspirin is the data that suggests that it might work as an anti-metastatic agent. There is data that shows that aspirin may be effective in reducing the risk of metastatic spread in breast, prostate and colon cancer (for example this recent meta-analysis reported a relative risk of metastasis of 0.77 with aspirin).

That we’ve known about the anti-cancer potential of aspirin for a long time isn’t a surprise – but I have to admit to being surprised to come across a paper from 1977 arguing the case that aspirin might be an effective anti-metastatic drug. The paper is Aspirin for reducing cancer metastases? by Henschke, Luande and Choppala (J Natl Med Assoc. 1977 Aug;69(8):581-4). The paper is available open access (here), and while the data is old, the arguments it makes are still vital and relevant. It really begs the question, how is that things haven’t moved forward more quickly? And, more crucially, how can we make sure that things move forward more quickly in the future. Not just for aspirin but for so many of the other old drugs that have good data in their favour.

Wednesday, 23 November 2016

The Anticancer Fund is pleased to announce that on Tuesday 15th November 2016, the first patient was enrolled in a clinical trial called CUSP9v3 for recurrent glioblastoma at the Department of Neurosurgery, University Hospital of Ulm, Germany. This is a phase 1 clinical trial. The study treatment will be given to 10 patients to assess safety and tolerability.

Glioblastoma is the most frequent type of malignant brain tumour in adults. In Europe and North America, there are 3-4 new cases per 100,000 inhabitants per year. Even when all visible tumour is surgically removed, glioblastoma almost always returns within a year. Therefore, after surgery patients are treated with radiotherapy and chemotherapy. Despite this additional treatment, glioblastomas usually regrow and at some point can no longer be effectively treated, often resulting in death 1-2 years after the initial diagnosis.

"For decades, researchers have been looking for new experimental therapies for our patients with no real success yet" says Professor Marc-Eric Halatsch, the neurosurgeon leading the trial. "Together with Dr Richard Kast (USA), we sought to address the problem that glioblastomas usually find a way to escape the action of a single drug. In 2013, we teamed up with an international group of researchers to propose a treatment that would act on multiple mechanisms used by glioblastoma cells to grow. This treatment consists of 9 drugs that are currently on the market for other indications than cancer (‘repurposed’ drugs). These nine drugs have ancillary attributes that block several of the mechanisms glioblastoma cells use to grow. These drugs had remarkable effects in preventing growth of glioblastoma cells in preclinical studies. A clinical trial was warranted."

In addition to contributing to the design and set-up of the trial, the Anticancer Fund will provide €300,000 for this study. "This type of treatment is not developed by the pharma industry because the 9 drugs are from different companies and all are off-patent and mostly available as generics" says Lydie Meheus, director of the Anticancer Fund. "This implies that the treatment, if successful, will not generate substantial additional financial return for the manufacturers of the drugs. Since the treatment can benefit patients and the healthcare system, it must be developed with the support of philanthropy and governments."

Patients participating in the trial will receive CUSP9v3 for one year. When all patients have completed 2 months of treatment, a first analysis will be done on the safety and tolerability of the combined treatment.

If the combination is well tolerated, a larger multi-centre study will be initiated to evaluate the treatment’s efficacy.

Further information on the CUSP9v3 trial can be found on www.anticancerfund.org or on www.clinicaltrials.gov (NCT02770378).

Wednesday, 22 June 2016

Cesare Spadoni, founder of aPODD (accelerate Paediatric Oncology Drug Development), talks to Pan Pantziarka about the problems in drug development in children's cancers, and about the crowdfunding campaign to find a new treatment for Medulloblastoma.

Pan: What is the aPODD foundation aiming to do?Cesare: aPODD (accelerate Paediatric Oncology Drug Development) was set up with the mission to speed up the development of better and safer treatments for children with cancer. This is a cause that is very close to my heart. I lost my first daughter to cancer a few years ago. That is when I began thinking about doing something for children with cancer.

Obviously, you can have a positive impact on sick children and their families in many different ways. In my case, because of my professional background in drug development, I felt compelled to do something to address the major problem preventing any further clinical improvement for children and adolescents with cancer: the lack of therapeutic options and the delayed access to the most innovative treatments.

Specific anti-cancer drugs are not developed for younger patients because it is not profitable for industry to do so. This is an area where patients’ organisations may play a vital role. Drug repurposing is certainly an area we are very much interested in. By looking at existing drugs we may be in a position to identify possible new treatments much faster and at a fraction of the cost and risk of new drug development

Pan: How is this campaign different to others?Cesare: We are looking to identify a potential new treatment for Medulloblastoma, a rather aggressive form of brain cancer that is more frequent in children and adolescents. The current therapeutic options for this cancer are limited and very harsh, including high dose chemotherapy and radiotherapy. The impact on patients may be devastating as the lucky survivors may face severe health problems later in life.

For this project we are partnering with Healx, a company based in Cambridge (UK), which offers very advanced technologies and strong expertise in drug re-purposing. Healx is applying advanced computational biology tools, data analytics and machine learning to make sense of complex biological data sets and match those with the profiles of known drugs.

We are now in the process of finalising a list of drugs that we would like to test experimentally in Medulloblastoma cell lines in view of progressing further with the most promising ones.
We are very excited by these early results and we are really hope that this crowdfunding is successful so that we can proceed as fast as we can.